Not applicable
1. Field of the Invention
The present invention relates generally to methods of identifying in a living vessel an atherosclerotic plaque at risk of rupture or thrombosis. More particularly, the invention relates to such methods that include detecting sites of inflammation in a vessel wall exhibiting about 0.2xc2x0-5xc2x0 C. temperature elevation above adjacent or ambient vessel wall temperature. The invention also relates to intravascular and non-invasive devices for measuring vessel wall temperatures and detecting about 0.2-5xc2x0 C. temperature differences between regions of living vessel wall.
2. Description of the Related Art
Despite the declining age-specific mortality of coronary atherosclerosis, many people who feel well and have no known cardiovascular disease continue to die suddenly of a first myocardial infarction or cardiac arrest. An estimated 35% of these patients had neither symptoms nor a diagnosis of coronary artery disease (Casscells et al. Lancet 347:1147-1149 (1996); Falk et al. Circulation 92:657-671 (1995); Davies et al. Lancet 347:1422-1423 (1996); Falk et al. Am J Cardiol 63:114E-120E (1989)). Rupture and/or thrombosis of an atherosclerotic plaque is the immediate cause of most myocardial infarctions and strokes. Myocardial infarction is not predictable by presently available clinical means, which greatly hampers prognosis and treatment of patients suffering from cardiovascular disease (Fuster et al. Circulation 82:1147-1159 (1990); Davies et al. Brit Heart J 53:363-373 (1985); Libby, P. Circulation 91:2844-2850 (1995); Liuzzao et al. N Engl J Med 331:417-424 (1994); Itoh et al. Coronary Artery Disease 6:645-650 (1995); and Ridker et al. N Engl J Med 336:973-979 (1997)).
In most instances of myocardial infarction, cardiac arrest, or stroke, it is found that only one of the potential obstructions, or plaques, has in fact, ruptured, fissured, or ulcerated. The rupture, fissure, or ulcer causes a large thrombus or blood clot to form on the inside of the artery, which may completely occlude the flow of blood through the artery, thereby injuring the heart or brain. It is known that approximately one-half of the unstable coronary atherosclerotic plaques are in arteries with 50% or less luminal diameter narrowing. See, for example, Fuster, V., et al., N Engl J Med 326:242-250 and 310-318 (1992). These are lesions that are usually considered insignificant anatomically. Thus, it would be highly desirable if methods and devices were available to detect the unstable atherosclerotic plaque, independent of the degree of luminal diameter narrowing, and treat it before unstable angina and/or acute myocardial infarction and their consequences occur.
These culprit lesions, referred to as xe2x80x9cvulnerable,xe2x80x9d xe2x80x9cdangerous,xe2x80x9d xe2x80x9cunstablexe2x80x9d or xe2x80x9cat-riskxe2x80x9d plaques, have some unique histopathologic features. These features include: a lipid core containing a substantial amount of free and esterified cholesterol, and other necrotic debris; infiltrated macrophages (and less frequently lymphocytes, monocytes and mast cells); less abundant smooth muscle cells; and, consequentially, low content of collagen and other matrix proteins.
The lipid core characterizing most ruptured plaque is mainly a large pool of cholesterol resulting from insudation and from the release of the contents of foam cells following degradation of the cell wall. The low content of collagen and matrix proteins associated with at-risk plaque contributes to an important feature of the unstable plaquexe2x80x94the thin plaque cap. The release of matrix-digesting enzymes by the inflammatory cells is thought to contribute to plaque rupture. Small blood clots, particularly microthrombi, are also frequently found on non-ruptured but inflamed ulcerated plaque surfaces.
The rupture process is not completely understood, but it is known that the plaques most likely to rupture are those that have both a thin collagen cap (fibrous scar) and a point of physical weakness in the underlying plaque. Such points are thought to be located (as determined by modeling studies and pathologic analysis) at junctures where pools of cholesterol meet a more cellular and fibrous part of the plaque. It has been observed that plaques with inflamed surfaces or a high density of activated-macrophages and a thin overlying cap are at risk of thrombosis. Van der Wal, et al., Circulation 89:36-44 (1994); Shah, et al., Circulation 244 (1995); Davies, et al., Br Heart J 53:363-373 (1985); Farb, et al., Circulation 92:1701-1709 (1995); Van Damme, et al., Cardiovasc Pathol 3:9-17 (1994).
Identifying Vulnerable Plaque
The development of medically feasible techniques to identify those plaques that are most likely to rupture, thrombose or rapidly progress in severity of vascular stenosis is an area of intense investigative activity. Most of the techniques undergoing study at the present time focus on the histological features of dangerous plaque. Modalities such as intravascular ultrasound, which might identify plaque vulnerability on the basis of cap thinness has been proven to be incapable of identifying which plaques are at risk of rupturing (de Feytia et al. Circulation 92:1408-13 (1995). Perhaps this is because the average cap thickness at the time of rupture is estimated to be 50 xcexcm (Burke et al. N Engl J Med 336:1276-82 (1997); Mann et al. Circulation; 94:928-31 (1996); and Falk et al. id. (1995)).
Moreno et al. (Circulation Suppl 17:1-1016 (1998) employ NIR spectroscopy to correlate the NIR spectra of plaque with the histological features of thin fibrous cap, lipid pool, macrophages and calcium content in an atherosclerotic rabbit model.
In U.S. Pat. No. 5,935,075 (issued to Casscells, et al.) (U.S. patent application Ser. No. 08/717,449) some of the present inventors demonstrated for the first time that there is thermal heterogeneity in human atherosclerotic arteries and that inflamed plaques give off more heat than non-inflamed plaques. These inflamed regions, sometimes called xe2x80x9chotxe2x80x9d plaques, are regions of atherosclerotic plaque that exhibit temperatures that are elevated about 0.4-4.0xc2x0 C. above non-inflamed adjacent vessel wall temperature. Previously, local heat had not been identified in atherosclerosis and exploited for diagnosing vulnerable plaque based on the association of inflammation and macrophages with plaque rupture.
Recently, Stefanadis et al. (Circulation 99:1965-1971 (1999)) has reported a confirmatory study in patients suffering acute myocardial infarction showing substantial thermal heterogeneity (1.7xc2x0 C.) at points along their coronary arteries, as measured by a catheter-mounted thermistor in contact with the vessel wall.
U.S. Pat. No. 5,935,075 (Ser. No. 08/717,449) (Casscells et al.) also discloses a method of detecting heat-producing inflammatory cells at sites along a vessel wall using an infrared-sensing catheter, or other invasive or non-invasive temperature measuring devices. One exemplary catheter includes an infrared-transparent balloon enclosing a group of optical fibers.
U.S. Pat. No. 5,871,449 (issued to Brown) describes another infrared fiber optic catheter intended for measuring vessel wall temperature to reveal inflamed plaques. One problem with currently-available infrared optical fibers is that they are not made of biocompatible material, and are therefore unsuitable for directly contacting tissues and fluids inside a human blood vessel. Also, the somewhat brittle nature of conventional infrared optical fibers makes them incapable of bending sufficiently to be aimed directly into a plaque (i.e., perpendicular to the linear axis of the vessel). Infrared fiber optic catheter designs must also take into account the interference by blood, saline or other vessel fluids with the infrared signal.
Catheter-Based Temperature Sensing Devices
A number of devices and procedures have been employed to diagnose, treat or inhibit vascular obstructions, and in some of these devices a temperature sensing element is included. Most of these temperature sensing means are intended to monitor high-temperature heating of vascular lesions. Very few of these intravascular heat sensing devices are actually capable of, or practical for, discerning slight to moderate temperature elevations (i.e., 0.01xc2x0 C. or more) along the luminal wall of a vessel.
U.S. Pat. No. 5,057,105 relates to a hot tip catheter assembly for xe2x80x9cmeltingxe2x80x9d plaque. This device employs a thermocouple to continuously monitor the heating of the catheter tip in order to prevent overheating of the vessel wall.
The recent U.S. Pat. No. 5,775,338 (issued to Hastings) describes a heated perfusion balloon for reduction of restenosis by application of low-level heat to a site of arterial injury. For measuring the extent of heating of the vessel wall, a J-type thermocouple mounted on the outside of a balloon is pressed against the vessel wall to measure temperature relative to bloodstream temperature. The blood temperature is measured by another temperature sensor which is disposed upstream of the thermocouple sensor.
Most of the prior art methods and catheter-based heat sensing devices are unable to differentiate plaque from normal vessel wall, much less distinguish between unstable plaques and the more stable ones that are not at imminent risk of rupturing or occluding. Even when the presence or absence of histological features such as calcification in plaque can be assessed by one of the existing devices, it is not adequately predictive of whether the plaque is unstable or whether it will tend to rapidly progress in severity of vascular stenosis. It is very important to be able to detect the unstable atherosclerotic plaque independent of the degree of luminal diameter narrowing, and treat it before the unstable angina and/or acute myocardial infarction and their consequences occur.
Medical Infrared Thermography
Infrared thermography or radiometry (IR), has long been used for non-destructive testing in a wide range of industrial disciplines, such as determining the condition of selected electrical components, motors, metal fatigue, for example. Similar technology has also been widely employed for many years to make practical temperature measurements in military and medical fields by applying principles of infrared radiation and thermal imagery.
In the human body, heat is produced by metabolism. It is distributed by blood and the lymphatic system to the rest of the body, and particularly to the overlying skin. Heat is lost primarily by radiation and convection of the excessive heat energy through the skin and into the surrounding air. The IR radiation from the human body can be detected by the IR thermography. Correlating the temperature to the metabolic state of the body, one can obtain useful information about the diseased states of the body organs.
For example, U.S. Pat. No. 5,445,157 (Adachi et al.) describes a type of infrared thermographic endoscope for imaging a body cavity after injecting a low-temperature gas. U.S. Pat. No. 4,995,398 relates to the use of thermography during the course of by-pass heart surgery for the purpose of checking the success of the operation before closing the chest cavity. This patent describes the use of a scanning thermal camera, image processing, temperature differentials and displaying images in real-time. Stenoses at the sites of distal anastomoses are detected using a cold injectate, which when mixed with the warmer circulating blood, provides images which are captured by a thermal camera focused on the heart.
Several decades ago, IR thermography was investigated for detecting breast cancer. In these early studies, thermographic liquid crystals and infrared-sensitive film were used to record asymmetries in the venous drainage from the breasts. The veins in most people are close enough to the surface to be identifiable by thermal mapping techniques. Markedly asymmetric patterns often indicated the presence of breast lesions, in some cases before a symptom or palpable mass was evident. Infrared thermography did not have the sensitivity of x-ray mammography for deep masses, however, because the temperature of many such masses does not directly reach the skin. Also, many such masses do not create an obvious disturbance in the pattern of venous drainage.
Recent developments in thermal imaging detectors, semiconductors, and high speed computers and imaging software have enhanced the accuracy and sensitivity of infrared thermography, thus making it more attractive as a non-invasive tool for medical and diagnosis. Medical IR thermography today is a noninvasive diagnostic technique that allows the examiner to visualize and quantify changes in skin surface temperature, which maps the body temperature several mm deep to the skin, and is referred to as a thermogram (Cotton J Am Med Assoc 267:1885-1887 (1992)). Since there is a high degree of thermal symmetry in the normal body, subtle (0.02xc2x0 C.) temperature asymmetries can be identified quickly and an explanation can be sought. IR thermography has also been used recently in determining the level of amputation in patients with gangrene (McCollum et al. Br J Surg 75:1193-5[see comments] 1988; Spence et al. Prosthet Orthot Int 8:67-75 (1984); Spence et al. Angiology 32:155-69 (1981); Bergtholdt et al. Arch Phys Med Rehabil 56:205-9 (1975)). These surgeons found that a degree of coolness accurately demarcated nonviable tissue. Thermography has also been recently used by others to assess the completeness of revascularization during aortocoronary bypass surgery. In this procedure, an infrared camera is placed several feet over the open chest, and when the aorta is unclamped and normal blood flow is returned to the myocardium, the areas that have been revascularized promptly radiate warmth; whereas the ischemic areas remain cool. The grafts to these areas can then be adjusted to improve the flow (Saxena et al. Pediatr Surg Int 15:75-76 (1999); Merin et al. Cardiovasc Surg 3:599-601 (1995): Falk et al. J Card Surg 10:147-60 (1995); Lawson et al. Am J Cardiol 72:894-6 (1993). Despite this work, infrared is little-used clinically today, and workable IR catheters have not been developed, due at least in part to the large size, brittleness and expense of commercially available IR optical fibers.
There are a number of commercially available catheters that monitor blood temperature in order to measure cardiac output (e.g. American Edwards/Baxter Swan Ganz catheter) by continuous thermo-dilution, but these catheters cannot measure the temperature of the vessel wall itself, or of specific plaque regions on the vessel wall.
Of the existing catheter-based and non-invasive methods and devices, none have proved to be adequate or practical for clinical use to identify unstable atherosclerotic plaques. What is needed are better ways to distinguish the dangerous plaques from the relatively more stable ones, regardless of their degree of luminal narrowing. Also needed are ways to detect specific arterial sites that are at risk for arterial restenosis after angioplasty or atherectomy.
The present invention overcomes many of the failures of the prior art by providing a sensitive method of identifying vulnerable or at-risk atherosclerotic plaque in a vessel. Moreover, the methods of the invention are able to distinguish such vulnerable plaques from the relatively stable plaques by detecting regions of elevated temperature along the vessel wall as an indicator of populations or clusters of activated inflammatory cells. An important advantage of the present methods is that they assist the physician in diagnosing plaques at imminent risk of rupturing or occluding so that appropriate interventional steps may be taken to avert a possibly fatal cardiovascular event. Certain embodiments of the invention also permit the physician to monitor the condition of grafts and transplants so that the influx of inflammatory cells and the development of transplant vasculopathy can be detected and treated before the occurrence of a critical event.
In addition, new devices are disclosed which are useful for carrying out the minimally or non-invasive methods of the invention. Preferred exemplary devices include an infrared-sensing fiber optic bundle catheter and a thermocouple basket catheter, each of which is capable of detecting slight to moderate temperature differences between identifiable regions of a vessel. Such temperature differences are primarily in the range of about 0.2-5.0xc2x0 C., particularly the 0.4-4.0xc2x0 C. range, with plaques often exhibiting temperature differences of about 1.5xc2x0 C. or more.
The methods and devices of the present invention are also useful in predicting the behavior of injured blood vessels in medical patients, such as identifying specific arterial sites at risk for arterial restenosis after angioplasty or atherectomy, or identifying which patients are at risk due to vasculopathy, or tissue rejection.
The devices and methods of the present invention also are capable of effectively identifying patients who have arterial wall areas of unusually low temperature and which represent previously undetected arterial at-risk areas. Just as excess heat can identify regions at risk due to inflammation, sub-normal heat (i.e., areas cooler than the rest of a vessel) indicates a lack of actively metabolizing healthy cells, since heat in the body results from actively metabolizing cells. Non-cellular areas are typically regions of hemorrhage, thrombosis, cholesterol pools, or calciumxe2x80x94all indicators of high risk plaques. The devices and methods of the invention achieve these ends by identifying and analyzing thermal discrepancies in the wall temperature of blood vessels, in some embodiments of the invention, devices are provided that are also capable of providing a thermal image of the vessel wall and of applying therapeutic gentle heat treatment.
In accordance with the present invention, a method is provided for detecting along a vessel wall an atherosclerotic plaque that is at risk of reducing the flow of fluid within the vessel. The method includes determining whether a plaque exhibits an elevated temperature compared to a predetermined baseline temperature, such as an average vessel wall temperature.
Also in accordance with the invention is a method of identifying in a living vessel an atherosclerotic plaque at risk of rupture or thrombosis. The method comprises measuring the temperature of at least two sites along the lumen wall of a vessel in a living subject and detecting a temperature elevation of about 0.2 to 5xc2x0 C. at one site relative to the temperature of at least one other site along the vessel.
In certain embodiments of the methods of the invention an average or ambient vessel wall temperature is established and a 0.4 to 4xc2x0 C. temperature difference is assessed between one site and the average or ambient vessel wall temperature. In some embodiments the temperature difference detected is about 0.2-2.5xc2x0 C., and preferably a temperature difference of at least about 1.5xc2x0 C. is detected in at-risk plaque.
In preferred embodiments of the methods a heat detecting catheter assembly is introduced into a vessel of a living subject to identify at-risk plaque. In some embodiments the heat detecting catheter of the assembly is an infrared imaging catheter that has a flexible housing enclosing a flexible imaging bundle. The infrared imaging bundle contains a plurality of coherent optical fibers that are, a circumferential window in the housing that is designed for contacting a vessel wall. Also enclosed by the catheter housing is a reflective surface is in xe2x80x9coptical communicationxe2x80x9d with both the window and the optical fibers. This means that optical radiation emitted from the vessel wall is received by the reflective surface and directed into the fibers. Likewise, optical radiation emitted from the fibers is received and reflected by the reflective surface and directed onto the vessel wall. Also enclosed by the catheter housing is a lumen that can accommodate either a guidewire or a flushing fluid for washing the occluded vessel ahead of the catheter. The catheter assembly employed in the methods may also include a guiding catheter that has an inflatable occluding balloon, an inflation lumen and a special lumen for receiving or guiding the infrared catheter.
In certain alternative embodiments of the methods a heat detecting catheter that employs a thermocouple basket catheter is introduced into the vessel. In some of these the thermocouple basket have a point of maximum outer diameter when deployed, at least one channel containing a pair of electrically insulated thermocouple wires, and a thermocouple junction situated at said maximum diameter point and disposed inside said channel between a thermally conductive layer and a thermally insulating layer. Some embodiments include an intravascular ultrasound wire (IVUS) for obtaining an ultrasound image in conjunction with obtaining a thermal map of a vessel wall.
Certain other embodiments of the methods introduce a thermistor basket catheter into the vessel. In some of these thermistor basket catheter embodiments the basket has a point of maximum outer diameter when deployed and at least one channel containing a resistive temperature device situated at said maximum diameter point.
Still other alternative embodiments of the methods involve introducing a catheter chosen from the group consisting, of intravascular ultrasound, intravascular magnetic resonance imaging, liquid crystal coated balloon catheter thermometry and catheter-based near-infrared spectroscopy.
Also in accordance with the present invention are non-invasive methods for detecting at-risk plaque. Some of these include measuring the temperature of at least two sites along the vessel wall using infrared, microwave, or magnetic resonance imaging.
The present invention further provides an infrared imaging catheter that comprises a flexible housing enclosing a flexible imaging bundle. The imaging bundle contains a plurality of coherent optical fibers, preferably about 900. The imaging bundle is arranged around a guidewire/flushing lumen that extends lengthwise through the catheter. There is a window in the housing that extends around the circumference of the catheter and is made for contacting the vessel wall. A reflective surface, such as a mirror, is in optical communication with the window and the optical fibers.
An intravascular infrared imaging catheter assembly for detecting temperature heterogeneity along a vessel wall is also provided by the present invention. One embodiment of this assembly includes the above-described IR catheter and also has a guiding catheter for receiving the IR catheter in such a way that the IR catheter can slide within the lumen of the guiding catheter. The guiding catheter also has an inflatable occluding balloon and an inflation lumen connected to the balloon. In some embodiments an ultrasound wire or transducer is located in the guidewire flushing lumen, so that ultrasound examination of the vessel wall can be conducted in conjunction with the temperature sensing. In some embodiments means are included in the catheter assembly for applying 38xc2x0 to 45xc2x0 C. heat to discrete regions of vessel wall.
An infrared imaging catheter in accordance with the invention may also include an infrared array detector, a signal processor, a microcontroller programmed for receiving, storing, analyzing and reporting temperature information obtained from a plurality of sites along a vessel wall, a display system, such as a computer monitor, and a user interface such as a keyboard. The catheter is in optical contact with the infrared array detector. The detector is in electronic contact with the signal processor, and the signal processor is in electronic contact with the display system and the microcontroller. The microcontroller, which may be a personal computer, is also in electronic contact with the user interface.
In some embodiments, particularly those incorporating a heating modality, the assembly also has an infrared radiation source in optical communication with an infrared fiber multiplexer. In this case, the multiplexer is also in electrical contact with the microcontroller.
A thermocouple basket catheter according to the invention also provides for detecting temperature heterogeneity along a vessel wall. Certain embodiments of this catheter comprise an expandable basket formed by at least two hollow channels that have proximal and distal end. Each of these channels contains a thermally conductive material, and each channel has a vessel wall-contacting side and a vessel lumen facing side. A hollow shaft is joined to the proximal end of the basket and a tip is joined to the basket""s distal end. A thermocouple junction is situated inside each channel, with the junction being situated along the length of each channel at a point about mid-way between the basket""s proximal and distal ends. Inside each channel, the junction is situated xe2x80x9coff centerxe2x80x9d so that it is in thermal contact with the side of the channel that touches the vessel wall. The junction is away from, and thermally insulated from, the lumen facing side of the channel. The two insulated thermocouple wires inside each channel extend from the junction through the hollow shaft of the catheter. The basket also includes a tip that encloses the distal end of each channel. The channel ends may be either fixed securely inside the tip or they may be able to move back and forth inside the tip.
One embodiment of an intravascular thermocouple catheter assembly for detecting temperature heterogeneity along a vessel wall contains the above-described thermocouple basket catheter and a guiding catheter with a guiding lumen adapted for slidingly receiving the thermocouple basket catheter. In some embodiments the guiding catheter has an inflatable occluding balloon and an inflation lumen in communication with the balloon. Certain embodiments include a thermally insulating material disposed inside each of the channels between the junction and the lumen-facing side of the channel.
Another catheter embodiment of the invention is a thermistor basket catheter. An expandable basket is formed by at least four hollow channels, each channel having a vessel wall-contacting side and a lumen facing side. A hollow shaft is joined to the proximal end of the basket and a tip is connected to the basket""s distal end. On each channel a thermistor is situated on the outside of each of the channels, and placed longitudinally on each channel at about the point of maximum deployment for each channel on the vessel contacting side of the channel. A pair of insulated wires in electrical contact with the thermistor extends from the thermistor through the hollow shaft.
Certain preferred embodiments of the catheters of the present invention have an outer diameter of no more than about 6 mm, and in some embodiments the diameter is no more than 3 mm.
One preferred assembly for identifying vulnerable atherosclerotic plaque includes an infrared catheter having an external diameter of no more than 6 mm. This catheter includes a flexible housing that encloses a flexible imaging bundle containing a plurality of coherent optical fibers. The bundle is disposed about a guidewire/flushing lumen that extends lengthwise through the catheter. There is a circumferential window in the housing that is designed for contacting the vessel wall. A reflective surface, such as a conical mirror is in optical communication with both the window and the optical fibers. The assembly also includes a guiding catheter with an inflatable occluding balloon, an inflation lumen connected to the balloon, and a guiding lumen designed for receiving the imaging catheter in such a way that the catheter slides through the guiding lumen. The assembly also includes an infrared array detector, a signal processor, a microcontroller programmed for receiving, storing, analyzing and reporting temperature information obtained from a plurality of sites along a vessel wall, a display system and a user interface. The optical fibers are in optical contact with the infrared array detector, and the detector is in electrical contact with the signal processor. The signal processor is in electrical contact with the display system and the microcontroller. The microcontroller is in electrical contact with the user interface. In an alternative embodiment the assembly also includes an infrared radiation source in optical communication with an infrared fiber multiplexer, and the multiplexer is also in electrical contact with the microcontroller.
Another assembly for identifying vulnerable atherosclerotic plaque, which is provided by the invention, employs one of the thermocouple or thermistor catheters of the invention, a suitably programmed microprocessor capable of receiving, storing, analyzing and reporting temperature information, a temperature display system, and a user interface.
A method of detecting and monitoring inflammation in a transplanted arteriovenous (AV) graft in a living subject is also provided by the invention. This method comprises using an infrared camera and non-invasively imaging said arteriovenous graft to obtain an initial infrared thermogram of the AV graft. After obtaining an initial infrared thermogram, the infrared imaging is repeated to obtain a second infrared thermogram of the graft. After the second thermogram, the infrared imaging is optionally repeated to obtain at least one subsequent infrared image of the graft. The initial, second and subsequent infrared images are then compared to identify temperature changes in a region of the graft. From the observed temperature changes, an increase, decrease or no change in inflammation is determined for at least one region of the graft.
The invention further provides a method of evaluating an anti-atherosclerotic interventional therapy in a flowing mammalian artery. This method includes producing an animal model of human atherosclerosis by feeding cholesterol to a Watanabe heritable hypercholesterolemic rabbit such that visible, palpably warm atherosclerotic lesions extending along the central ear artery of the rabbit develop. The temperature of at least one region of the ear artery is then measured non-invasively to obtain at least one baseline temperature measurement. Preferably the non-invasive temperature measurement is done with an infrared imaging camera. An anti-atherosclerotic interventional treatment it then administered to at least one said animal model. A suitable control treatment is similarly administered to at least one said animal model. Subsequent to said treatments, the temperature of at least one region of rabbit artery in at least one said treated animal model is non-invasively measured to obtain at least one post-treatment temperature measurement. The method further includes comparing the baseline, control and post-treatment temperature measurements, and detecting any temperature differences in an artery attributable to the interventional treatment.
Also according to the present invention a method of monitoring the progression or amelioration of an atherosclerotic plaque in a flowing mammalian artery is provided. This method comprises breeding genetically hypercholesterolemic animals characterized by development of atherosclerotic lesions that are histologically similar to human atherosclerotic plaques, whereby an animal model of human atherosclerosis is produced. Employing a heat-detecting catheter of the invention, the temperature of a multiplicity of sites along a vessel wall of the animal is measured, in order to obtain a baseline temperature measurement for each of the sites. The physical location of each such site along the vessel wall corresponding to each respective temperature measurement is recorded. The catheter is then removed from the vessel of the animal. At a later time, the same or a similar catheter is reinserted and the temperature measurement and recording of physical location are repeated. Any temperature difference between adjacent sites of the vessel wall and for any temperature difference between each site and its corresponding baseline temperature are then determined.
The invention""s methods and devices will have a number of utilities, including reduction of morbidity and mortality from coronary and carotid artery atherosclerosis, reduction of restenosis and thus the need for repeated angioplasties or atherectomies, and also including reduction of vasculopathy in organ-transplant patients. In turn, these improved outcomes will produce the benefits of better health care, improved public health, and reduced health care costs. These and other objects, features and advantages of the present invention will become apparent with reference to the following description and drawing.